The long-term goal of the proposed research is to provide non- toxic prolyl-4-hydroxylase inhibitors for use in the treatment of diseases associated with the overproduction of collagen: fibroses of lung and liver, hepatic cirrhosis, scleroderma and especially conditions associated with atherosclerosis and other abnormalities of the circulatory system. There are currently no clinical agents in use which selectively inhibit prolyl-4-hydroxylase, the enzyme responsible for the rate-determining step of collagen biosynthesis. Certain C-glycosyl anthraquinone natural products are potent hydroxylase inhibitors; a concise and simple methodology for the preparation of these compounds is proposed. Research results and methodology which has been developed in our lab will be used for a short enantiospecific total synthesis of vineomycinone B2, a representative C-glycosyl anthraquinone. Analogs will also be prepared for testing for hydroxylase inhibition in collaboration with Dr. James Willerson's group (University of Texas Health Science Center, Dallas) and for cytotoxicity in this Department in collaboration with Dr. Gregory Patterson. New, very efficient methods have been developed in these laboratories to simultaneously solve both problems posed by the synthesis of C-glycosyl anthraquinones: by performing an aromatic annelation reaction on a sugar derivative, the substituted anthraquinone ring and the C-glycoside can be formed in a single step. This makes an extremely expeditious synthesis of the vineomycins and their analogs possible.